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Study of Ipatasertib or GDC-0980 With Abiraterone Acetate Versus Coralie in Participants With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel Chemotherapy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01485861
First received: December 2, 2011
Last updated: March 20, 2017
Last verified: March 2017
  Purpose
This multicenter, international, Phase Ib/II trial consists of two stages: a Phase Ib, open-label stage in which the recommended Phase II dose will be determined for ipatasertib and GDC-0980 in combination with abiraterone and prednisone/prednisolone and a Phase II, 3-arm, double-blind, randomized comparison of ipatasertib with abiraterone and prednisone/prednisolone versus placebo with abiraterone and prednisone/prednisolone.

Condition Intervention Phase
Prostate Cancer
Drug: Abiraterone
Drug: GDC-0980
Drug: Ipatasertib
Drug: Placebo
Drug: Prednisone
Drug: Prednisolone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study of GDC-0068 or GDC-0980 With Abiraterone Acetate Versus Abiraterone Acetate in Patients With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Phase Ib: Percentage of Participants With Dose Limiting Toxicity (DLTs) [ Time Frame: Days 1 to 28 of Cycle 1 (Cycle length = 28 days) ]
  • Phase Ib: Percentage of Participants by Nature of DLTs [ Time Frame: Days 1 to 28 of Cycle 1 (Cycle length = 28 days) ]
  • Phase Ib: Recommended Phase II Dose (RP2D) of Ipatasertib [ Time Frame: Days 1 to 28 of Cycle 1 (Cycle length = 28 days) ]
  • Phase II: Percentage of Participants With Radiographic Progression (as Assessed by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) or Death - Intent to Treat (ITT) Population [ Time Frame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Radiographic Progression Free Survival as Assessed by RECIST 1.1 - ITT Population [ Time Frame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Percentage of Participants With Radiographic Progression (as Assessed by RECIST 1.1) or Death in Participants With Institute of Cancer Research (ICR) Phosphatase and Tensin Homolog (PTEN) Loss [ Time Frame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Radiographic Progression Free Survival (as Assessed by RECIST 1.1) in Participants With ICR PTEN Loss [ Time Frame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]

Secondary Outcome Measures:
  • Phase II: Percentage of Participants Who Died - ITT Population [ Time Frame: Screening up to death (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Overall Survival - ITT Population [ Time Frame: Screening up to death (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Percentage of Participants Who Died in Participants With ICR PTEN Loss [ Time Frame: Screening up to death (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Overall Survival in Participants With ICR PTEN Loss [ Time Frame: Screening up to death (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Percentage of Participants With Prostate-Specific Antigen (PSA) Progression (as Assessed by Prostate Cancer Working Group 2 Criteria) - ITT Population [ Time Frame: Screening up to PSA progression (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Time to PSA Progression (as Assessed by Prostate Cancer Working Group 2 Criteria) - ITT Population [ Time Frame: Screening up to PSA progression (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Percentage of Participants With PSA Progression (as Assessed by Prostate Cancer Working Group 2 Criteria) in Participants With ICR PTEN Loss [ Time Frame: Screening up to PSA progression (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Time to PSA Progression (as Assessed by Prostate Cancer Working Group 2 Criteria) in Participants With ICR PTEN Loss [ Time Frame: Screening up to PSA progression (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Percentage of Participants With PSA Response - ITT Population [ Time Frame: Baseline, Day 1 of every cycle (starting from Cycle 2) till 30 days after last dose (up to overall 3.6 years) (cycle length = 28 days) ]
  • Phase II: Percentage of Participants With PSA Response in Participants With ICR PTEN Loss [ Time Frame: Baseline, Day 1 of every cycle (starting from Cycle 2) till 30 days after last dose (up to overall 3.6 years) (cycle length = 28 days) ]
  • Phase II: Percentage of Participants With Objective Response as Assessed by RECIST 1.1 - ITT Population [ Time Frame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Percentage of Participants With Objective Response (as Assessed by RECIST 1.1) in Participants With ICR PTEN Loss [ Time Frame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Duration of Tumor Response, as Assessed by RECIST 1.1 - ITT Population [ Time Frame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  • Phase II: Percentage of Participants With Circulating Tumor Cells (CTC) Reduction Response - ITT Population [ Time Frame: Screening, on Day 1 of Cycle 2, on Day 1 of Cycle 3, and at the treatment completion visit (up to overall 3.6 years) (cycle length=28 days) ]
  • Phase II: Percentage of Participants With CTC Reduction Response in Participants With ICR PTEN Loss [ Time Frame: Baseline, on Day 1 of Cycle 2, on Day 1 of Cycle 3, and at the treatment completion visit (up to overall 3.6 years) (cycle length=28 days) ]
  • Phase II: Percentage of Participants With CTC Conversion - ITT Population [ Time Frame: Baseline, on Day 1 of Cycle 2, on Day 1 of Cycle 3, and at the treatment completion visit (up to overall 3.6 years) (cycle length=28 days) ]
  • Phase II: Percentage of Participants With CTC Conversion in Participants With ICR PTEN Loss [ Time Frame: Baseline, on Day 1 of Cycle 2, on Day 1 of Cycle 3, and at the treatment completion visit (up to overall 3.6 years) (cycle length=28 days) ]
  • Phase II: Percentage of Participants With Pain Progression - ITT Population [ Time Frame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years) ]
  • Phase II: Time to Pain Progression - ITT Population [ Time Frame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years) ]
  • Phase II: Percentage of Participants With Pain Progression in Participants With ICR PTEN Loss [ Time Frame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years) ]
  • Phase II: Time to Pain Progression in Participants With ICR PTEN Loss [ Time Frame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years) ]
  • Phase Ib: Maximum Plasma Concentration (Cmax) (in nanograms per milliliter [ng/mL]) of Ipatasertib and GDC-0980 When Co-Administered With Abiraterone [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  • Phase Ib: Time to Cmax (tmax) (in hours) of Ipatasertib and GDC-0980 When Co-Administered With Abiraterone [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  • Phase Ib: Area Under The Concentration Time Curve From Time 0 to 24 Hours (AUC0-24) (in ng/mL*hours) of Ipatasertib and GDC-0980 When Co-Administered With Abiraterone [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  • Phase Ib: Total Body Clearance (CL/F) of Ipatasertib When Co-Administered With Abiraterone [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Day 15 of Cycle 1 (cycle length=28 days) ]
  • Phase Ib: Accumulation Ratio of Ipatasertib When Co-Administered With Abiraterone [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  • Cmax of G-037720 (Metabolite of Ipatasertib) [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  • tmax of G-037720 (Metabolite of Ipatasertib) [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  • Phase Ib: AUC0-24 of G-037720 (Metabolite of Ipatasertib) [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  • Phase Ib: Accumulation Ratio of G-037720 (Metabolite of Ipatasertib) [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  • Phase Ib: Cmax of Abiraterone When Co-Administered With Ipatasertib or GDC-0980 [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  • Phase Ib: tmax of Abiraterone When Co-Administered With Ipatasertib or GDC-0980 [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  • Phase Ib: AUC0-24 of Abiraterone When Co-Administered With Ipatasertib or GDC-0980 [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  • Phase Ib: Plasma Half-Life of Abiraterone When Co-Administered With Ipatasertib or GDC-0980 [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  • Phase Ib: Accumulation Ratio of Abiraterone When Co-Administered With Ipatasertib or GDC-0980 [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]

Enrollment: 273
Actual Study Start Date: January 11, 2012
Estimated Study Completion Date: June 30, 2017
Primary Completion Date: September 1, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase Ib: Ipatasertib 400 mg + abiraterone
Participants will receive ipatasertib 400 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg twice daily (bid) continuously in 28-day treatment cycles until disease progression or intolerable toxicity.
Drug: Abiraterone
Orally once daily
Drug: Ipatasertib
Orally once daily
Drug: Prednisone
Orally bid
Drug: Prednisolone
Orally bid
Experimental: Phase Ib: GDC-0980 30 mg + abiraterone
Participants will receive GDC-0980 30 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg twice daily (bid) continuously in 28-day treatment cycles until disease progression or intolerable toxicity.
Drug: Abiraterone
Orally once daily
Drug: GDC-0980
Orally once daily
Drug: Prednisone
Orally bid
Drug: Prednisolone
Orally bid
Experimental: Phase II: Ipatasertib 400 mg + abiraterone
Participants will receive Ipatasertib 400 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg bid continuously in 28-day treatment cycles until disease progression or intolerable toxicity.
Drug: Abiraterone
Orally once daily
Drug: Ipatasertib
Orally once daily
Drug: Prednisone
Orally bid
Drug: Prednisolone
Orally bid
Experimental: Phase II: Ipatasertib 200 mg + abiraterone
Participants will receive Ipatasertib 200 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg bid continuously in 28-day treatment cycles until disease progression or intolerable toxicity.
Drug: Abiraterone
Orally once daily
Drug: Ipatasertib
Orally once daily
Drug: Prednisone
Orally bid
Drug: Prednisolone
Orally bid
Placebo Comparator: Phase II: Placebo + abiraterone
Participants will receive placebo (for Ipatasertib) once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg bid continuously in 28-day treatment cycles until disease progression or intolerable toxicity.
Drug: Abiraterone
Orally once daily
Drug: Placebo
Orally once daily
Drug: Prednisone
Orally bid
Drug: Prednisolone
Orally bid

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed metastatic or advanced prostate adenocarcinoma that has been previously treated with docetaxel and has progressed during treatment of at least one hormonal therapy
  • Two rising PSA levels greater than or equal to (>/=) 2 ng/mL measured >/= 1 week apart or radiographic evidence of disease progression in soft tissue or bone
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening
  • Adequate hematologic and organ function
  • Documented willingness to use an effective means of contraception

Exclusion Criteria:

  • History of Type I or Type II diabetes mellitus requiring insulin
  • New York Heart Association Class III or IV heart failure or Left ventricular ejection fraction < 50% or ventricular arrhythmia requiring medication
  • Significant atherosclerotic disease, as evidenced by: unstable angina, history of myocardial infarction within 6 months prior to Day 1, or cerebrovascular accident within 6 months prior to Day 1
  • Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs or active inflammatory disease which requires immunosuppressive therapy
  • Clinically significant history of liver disease
  • History of adrenal insufficiency or hyperaldosteronism
  • Phase II only: Previous therapy for prostate cancer with 17 alpha-hydroxylase/C17,20-lyase inhibitors, including abiraterone
  • Phase II only: Previous treatment for prostate cancer with Protein kinase B phosphatidylinositol 3 kinase and/or mammalian target of rapamycin inhibitors
  • Need for chronic corticosteroid therapy of >/= 20 mg of prednisone per day or an equivalent dose of other anti inflammatory corticosteroids or immunosuppressant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01485861

  Show 64 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01485861     History of Changes
Other Study ID Numbers: GO27983
2011-004126-10 ( EudraCT Number )
Study First Received: December 2, 2011
Last Updated: March 20, 2017

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Docetaxel
Prednisone
Abiraterone Acetate
Prednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Steroid Synthesis Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 27, 2017